A growing body of evidence indicates that environmental information can be transmitted from parents to progeny. Thus, epigenetic changes in the mammalian germline can act as transgenerational carriers of environmental perturbations. Cocaine addiction remains a significant health problem in the United States and chronic cocaine use is associated with neurocognitive deficits. However, it remains unclear whether cocaine abuse in parents translates to reduced cognitive function in their offspring. This proposal will focus on the effects of paternal cocaine taking on memory formation in offspring using a rat model of cocaine addiction. We found that offspring and grand-offspring of cocaine-exposed fathers (sires) have spatial learning deficits and impaired hippocampal synaptic plasticity. In Specific Aim 1, we hypothesize that increasing NMDA receptor signaling will ameliorate learning and synaptic plasticity deficits caused by paternal cocaine taking. In Specific Aim 2, we will evaluate basal synaptic function, NMDA receptor signaling and epigenetic processes in the hippocampus of the descendants of cocaine-exposed sires. Taken together, this proposal will attempt to illuminate the mechanisms underlying learning deficits that are caused by paternal cocaine taking.